Bromine → 3-Bromo-5-methyl-4-methoxyphenylacetic acid

To a solution of 4-methoxy-3-methylphenylacetic acid (0.43 g) in glacial acetic acid (7 mL) was added 0.2 mL of neat bromine carefully while stirring. The mixture was stirred in dark at ambient temperature for 27 h. The resulting mixture was diluted with brine, extracted with ethyl acetate, dried and concentrated in vacuo to afford 3-bromo-5-methyl-4-methoxyphenylacetic acid. This crude product was dissolved in methanol (30 mL), treated with concentrated sulfuric acid (1 mL) carefully, stirred at reflux for 16 h. Cooled reaction mixture was concentrated under reduced pressure, diluted with brine, extracted with ethyl acetate. The combined organic layers were dried and concentrated in vacuo. The residue was dissolved in dichloromethane (10 mL), treated-with boron tribromide (1 M, 2 mL) under nitrogen and stirred at ambient temperature for 1 h. The reaction mixture was poured to stirring water and extracted with ethyl acetate from 1 N HCl. The combined organic layers were dried and concentrated. Flash column chromatography on silica gel with ethyl acetate/hexane (0-50% gradient elution) afforded 3-bromo-5-methyl-4-hydroxyphenylacetic acid methyl ester (0.21 g, 34%).

1. stirringThe mixture was stirred in dark at ambient temperature for 27 h
2. extractionextracted with ethyl acetate
3. customdried
4. concentrationconcentrated in vacuo

ORD record

ord-0592dfa0f0f74187985827f26bcd3f56

Source dataset

uspto-grants-2002_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06465687B1